Tissue-Specific Metabolic Response to Injury

烧伤会产生一系列戏剧性的生理和生化变化，包括：(1) 能量需求高于正常代谢率；(2)葡萄糖利用和蛋白质合成的变化；(3)流向烧伤区域和未受影响器官的血液变化；(4)创伤部位和多个其他器官的组织通透性增加。使用侵入性技术，这些过程中的许多已经在动物的器官和组织水平上进行了研究；然而，对人类的研究更加有限，要么涉及全身测量，要么涉及有限数量的器官的测量。在过去的资金周期中，我们使用PET方法开发、验证和应用了新的方法来测量各种组织中的血流量、血容量、氧利用和葡萄糖代谢以及骨骼肌中的蛋白质合成/降解。最近，我们开发了一种设备，用于在危重患者的床边进行其中一些测量。使用这些新的方法和标准技术，本项目将评估的假设是：(1)骨骼肌的组织特定能量需求低于正常水平，但肝脏和心脏的组织特定能量需求比正常水平高3-4倍。(2)葡萄糖以正常速率或低于正常速率被吸收到骨骼肌中，并进行厌氧糖酵解以产生乳酸。 丙氨酸和少量能量。(3)肌肉中的蛋白质合成处于或低于正常水平，这些速率可以被合成代谢因子改变。为了解决这些问题，我们将测量：(1)健康受试者和烧伤患者各种组织中的局部能量代谢；(2)烧伤患者骨骼肌蛋白质合成率；(4)烧伤患者骨骼肌及其他组织中葡萄糖和脂肪酸代谢的变化；(4)烧伤后骨骼肌和其他组织中的葡萄糖和脂肪酸代谢。为了更好地了解PET测量葡萄糖和脂肪酸利用与底物氧化之间的关系，将在烧伤和对照兔身上同时进行[U-14C]葡萄糖和[1-14C]棕榈酸酯代谢命运的稳态动力学研究。

Burn injuries produce a dramatic array of physiological and biochemical alterations, including: (1) increased energy requirements above the normal metabolic rate; (2) changes in glucose utilization and protein synthesis; (3) changes in blood flow to both the burned area and unaffected organs; and (4) increased tissue permeability at the site of trauma and in multiple other organs. Using invasive techniques, many of these processes have been studied at the organ and tissue level in animals; however, studies in humans are more limited and have involved either whole body measurements or measurements on a restricted number of organs. During the past funding cycle, using PET methods, we have developed, validated and applied new procedures for measuring blood flow, blood volume oxygen utilization and glucose metabolism in a variety of tissues and protein synthesis/degradation in skeletal muscle. Recently, we developed a device for performing some of these measurements at the bedside in critically ill patients. Using these new methods and standard techniques, the hypotheses to be evaluated in this project are: (1) There are tissue-specific energy requirements that are below normal levels in skeletal muscle but 3-4 fold higher in liver and heart. (2) Glucose is taken up into skeletal muscle at or below normal rates and undergoes anaerobic glycolysis to produce lactate alanine and little energy. (3) Protein synthesis is at or below normal levels in muscle and these rates can be modified by anaboli factors. To address these issues, we will measure: (1) regional energy metabolism in various tissues of healthy subjects and patients with burn injuries >15% BSA over the time course after injury; (2) skeletal muscle protein synthesis rates in burn patients; (3) the effects of Oxandrolone treatment on regional glucose metabolism and protein synthesis in convalescent burn patients; and (4) Glucose and fatty acid metabolism in skeletal muscle and other tissues of burned rabbits. To acquire a better understanding of the relationship between the PET measurements of glucose and fatty acid utilization and substrate oxidation, simultaneous steady-state kinetic studies of the metabolic fates of [U-14C] glucose and [1-14C] palmitate will be conducted in these burned and control rabbits.